Current Cancer Therapy Reviews - Volume 13, Issue 2, 2017

Background: Malignant mesothelioma is a largely incurable disease that is refractory to current therapies. CD26 is a multifunctional cell surface protein involved in autoimmune disease, diabetes, and cancer. It has a role in T cell function, extracellular protein modification, as a prognostic factor for cancer, and as a therapeutic target for malignant mesothelioma. New treatment strategies are urgently needed for malignant pleural mesothelioma (MPM), and CD26-targeted therapy represents a novel approach. Outline: In this review, the most current and up-to-date literature available was reviewed and the current state of malignant mesothelioma treatment is described. Throughout the review the need for new therapeutic approaches is highlighted in the shortcomings of current therapy. CD26 is a target that is fit to take on these shortcomings. In this review we discuss the structure and function of CD26, its role in malignant mesothelioma and the future of anti-CD26 therapy as a versatile immunotherapeutic option. Conclusion: This review highlights the areas of most promise in treating MPM, these include immune checkpoint blockade, passive immunization, and based on our recently published data, targeting of CD26 with its specific mAb. Finally we describe how the anti-CD26 mAb YS110 was recently evaluated in the first-in-human phase I clinical trial, showing prolonged disease stabilization and a favorable side effect profile. Through better understanding of CD26, new pathways to treating and potentially curing malignant mesothelioma may be discovered.

Background: Currently, existing regimens of genotoxic drugs have been suggested to be complemented with molecular inhibitors as combinatorial and cocktail approaches in malignancy. Methods: In the last decade, attempts have been reported to test several new class of anticancer drug such as miRNA mimetics, RNA enzymes, small molecular inhibitors, DNA repair protein inhibitors and peptide mimetics. Results: With the advent of rapidly growing genomic, epigenomic and proteomic data, design and application of peptide mimetics appear to thrive and sustain for an impactful cancer therapy. However, certain bottlenecks are envitable such as delivery of peptide mimetics drug in clinical settings, reducing the side effects, immune responses and pharmacokinetic properties. Conclusion: This review discusses emerging issues and potential avenues related to the scope and limitations of peptide mimetics in cancer treatment.

Background: Phosphodiesterase-5 (PDE5) inhibitors demonstrate off-label anticancer properties, acting through a variety of mechanisms that ultimately reduce tumor proliferation. Method: Combining PDE5 inhibitors with other anti-oncotic agents further enhances their effectiveness against tumors. Mechanistically, PDE5 inhibitors have been shown to inhibit ATP binding cassette (ABC) transporter protein activity, potentiate reactive oxygen species (ROS) activity, decrease FADD-like IL-1β-converting enzyme (FLICE)- inhibitory protein (c-FLIP) expression, increase blood-brain tumor barrier (BTB) permeability, and, when administered as a combination therapy, sensitize tumors to platinum. Conclusion: This review offers insights into the various mechanisms by which PDE5 inhibitors exert their antineoplastic actions.

Background: T cell activation via the blockade of PD-1 pathway has been recognized as an emerging drug target for cancer immunotherapy which provides a rationale for clinical trials in cancer patients. The recent breakthrough approvals of T cell checkpoint inhibitors targeting PD-1 pathway boost the era of immuno-oncology drugs. Methods: The progress of PD-1 checkpoint inhibitor as a single agent in the field of immuno-oncology is reviewed. Antibodies targting PD-1 and PD-L1 with regulatroy approvals are discussed with the current coverage of indications. Other candidates in clinical investigations are also summarized. Results: Monoclonal antibodies that block protein-protein interactions between PD-1 and its ligand have shown the promise for the treatment of a variety of cancer types. The fast growing family of PD-1 checkpoint inhibitors been observed both in regulatroy approvals and clinical investigations. Conclusion: The potential use of PD-1 checkpoint inhibitor alone or in combination with other agents is substantial, and will further reveal the important role of PD-1 pathway in immunomodulation and disease control.

Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. However, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect antimycin A3 and its analogue to induce apoptosis in those cells. Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer. Results and Conclusion: Open-chain analogues of antimycin A3 were successfully synthesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharpless asymmetric dihydroxylation. Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of antimycin A3 as a promising candidates of new anti-laryngeal cancer agents.